Background: Local anesthetics exert their anesthetic and analgesic effects by blocking the sodium channels in the nervous system. Phenothiazine-type antipsychotics also block sodium channels, but the local anesthetic characteristics of these drugs have not been evaluated. The aim of this study was to evaluate the cutaneous analgesic effect of phenothiazine-type antipsychotics. Methods: Using a subcutaneous injection model in rats, we tested the cutaneous analgesic effects of six phenothiazine-type antipsychotics (mesoridazine, promazine, chlorpromazine, fluphenazine, perphenazine and triflupromazine) at a dose of 0.6 μmol, and compared them with those of bupivacaine and lidocaine. A saline injection was used as the control. Results: All six phenothiazine-type antipsychotics elicited cutaneous analgesia. At the dose of 0.6 μmol, the potencies of mesoridazine and promazine were similar to that of bupivacaine; the other four drugs were less potent (p<0.001 for each comparison). Mesoridazine had a longer duration of action than bupivacaine (p<0.001). In terms of ED50 values, mesoridazine was more potent and longer-acting than bupivacaine and lidocaine (p<0.01 for each comparison). Conclusion: Of the antipsychotic drugs tested, mesoridazine is potentially the best candidate for development into a potent, long-acting local anesthetic. However, toxicity studies are needed before these agents can be used clinically as analgesics.
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